IFNγ induction of P21WAF1 in prostate cancer cells: Role in cell cycle and cell phenotype
Type I and type II interferons (IFNs) are known to exert antitumor effects on a variety of tissues and cell types. We have previously shown that the type I IFN IFNα induces the expression of the cyclin-dependent kinase inhibitor p21
WAF1 and inhibits the cell cycle of the human prostate adenocarcinoma cell line, DU145, that carries mutations in the tumor suppressor gene products p53 and pRB. We now show that the type II IFN IFNγ similarly induces the expression of p21
WAF1 and inhibits the cell cycle of DU145 cells. In addition, we show that while both IFNs exert antiproliferative activity, only IFNγ induced phenotypic changes in these cells that accompanied the antiproliferative effect. For example, IFNγ, but not IFNα, caused a significant reduction in EGF receptor expression as well as an increase in the adhesion molecules ICAM-1 and integrin α3. These phenotypic changes in DU145 cells are suggestive of the acquisition of a non-tumorigenic state. Consistent with these findings, IFNγ showed a significantly lower invasive ability in in vitro assays using invasion chambers. Thus, IFNγ inhibits both the cell cycle and the metastatic potential of DU145 cells independent of the p53 and pRB status, and these data describe a mechanism for mediating the antitumor capabilities of IFNγ that bypasses tumor suppressor genes like p53.
Hobeika, AC; Etienne, W; Cruz, PE; Subramaniam, PS; Johnson, HM
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